ation with magnesium. 7.3 antibiotics prior or concomitant use of antibiotics with clenpiq may reduce efficacy of clenpiq as conversion of sodium picosulfate to its active metabolite bhpm is mediated by colonic bacteria.

ids. if a patient develops significant vomiting or signs of dehydration including signs of orthostatic hypotension after taking clenpiq, consider performing post-colonoscopy lab tests (electrolytes, creatinine, and bun) and treat accordingly. approximately 20% of patients in both arms (sodium picosulfate, magnesium oxide, and anhydrous citric acid, or 2 l of peg + e plus two × 5-mg bisacodyl tablets) of clinical trials of another oral sodium picosulfate, magnesium oxide, and anhydrous citric acid product had orthostatic changes in blood pressure and/or heart rate on the day of colonoscopy and up to seven days post colonoscopy. in a single study of patients 9 to 16 years of age, approximately 20% of patients who received another oral product of sodium picosulfate, magnesium oxide, and anhydrous citric acid had orthostatic changes (changes in blood pressure and/or heart rate) compared with approximately 7% of those who received the comparator (peg) [see clinical studies (14) ] . these changes occurred up to five days post colonoscopy. fluid and electrolyte disturbances can lead to serious adverse reactions including cardiac arrhythmias or seizures and renal impairment. correct fluid and electrolyte abnormalities before treatment with clenpiq. in addition, use caution when prescribing clenpiq for patients who have conditions or who are using medications that increase the risk for fluid and electrolyte disturbances or that may increase the risk of seizure, arrhythmia, and renal impairment [see drug interactions (7.1) ] . 5.2 seizures there have been reports of generalized tonic-clonic seizures with the use of bowel preparation products in patients with no prior history of seizures. the seizure cases were associated with electrolyte abnormalities (e.g., hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia) and low serum osmolality. the neurologic abnormalities resolved with correction of fluid and electrolyte abnormalities. use caution when prescribing clenpiq for patients with a history of seizures and in patients at risk of seizure, such as patients taking medications that lower the seizure threshold (e.g., tricyclic antidepressants), patients withdrawing from alcohol or benzodiazepines, patients with known or suspected hyponatremia [see adverse reactions (6.2) ] . 5.3 use in patients with renal impairment as with other magnesium containing bowel preparations, use caution when prescribing clenpiq for patients with impaired renal function or patients taking concomitant medications that may affect renal function (such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or non-steroidal anti-inflammatory drugs) [see drug interactions (7.1) ] . these patients may be at increased risk for renal injury. advise these patients of the importance of adequate hydration before, during, and after the use of clenpiq. consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and bun) in these patients. clenpiq is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 ml/min), as accumulation of magnesium in plasma may occur [see contraindications (4) ] . 5.4 cardiac arrhythmias there have been rare reports of serious arrhythmias associated with the use of ionic osmotic laxative products for bowel preparation. use caution when prescribing clenpiq for patients at increased risk of arrhythmias (e.g., patients with a history of prolonged qt, uncontrolled arrhythmias, recent myocardial infarction, unstable angina, congestive heart failure, or cardiomyopathy). consider pre-dose and post-colonoscopy ecgs in patients at increased risk of serious cardiac arrhythmias. 5.5 colonic mucosal ulceration, ischemic colitis, and ulcerative colitis osmotic laxatives may produce colonic mucosal aphthous ulcerations and there have been reports of more serious cases of ischemic colitis requiring hospitalization. concurrent use of additional stimulant laxatives with clenpiq may increase this risk. consider the potential for mucosal ulcerations when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease [see adverse reactions (6.2) ] . 5.6 use in patients with significant gastrointestinal disease if gastrointestinal obstruction or perforation is suspected, perform appropriate diagnostic studies to rule out these conditions before administering clenpiq [see contraindications (4) ] . use with caution in patients with severe active ulcerative colitis. 5.7 aspiration patients with impaired gag reflex are at risk for regurgitation or aspiration during the administration of clenpiq. observe these patients during the administration of clenpiq.

dose: administer during evening before the colonoscopy second dose: administer the next day, during the morning prior to the colonoscopy. 2.1 important administration instructions correct fluid and electrolyte abnormalities before administration of clenpiq. clenpiq is ready to drink. it is a clear solution with possible presence of visible particles and it does not need to be diluted prior to administration. one bottle of clenpiq is equivalent to one dose. two doses of clenpiq are required for a complete preparation for colonoscopy as a split-dose regimen. the split-dose method consists of two separate doses: the first dose during the evening before the colonoscopy and the second dose the next day, during the morning prior to the colonoscopy [see dosage and administration (2.2) ] . additional liquids must be consumed after every dose of clenpiq: five or more 8-ounce cups of clear liquids after the first dose and four or more 8-ounce cups of clear liquids after the second dose [see dosage and administration (2.2) , warnings and precautions (5.1) ] . consume only clear liquids (no solid food) from the start of clenpiq treatment until after the colonoscopy. do not eat solid food or dairy and do not drink anything colored red or purple. do not drink alcohol. do not take other laxatives while taking clenpiq. do not take oral medications within one hour of starting clenpiq. if taking tetracycline or fluoroquinolone antibiotics, iron, digoxin, chlorpromazine, or penicillamine, take these medications at least 2 hours before and not less than 6 hours after administration of clenpiq. stop consumption of all liquids at least 2 hours before the colonoscopy. 2.2 split-dose dosage regimen the recommended dosage in adults and pediatric patients 9 years of age and older is shown below. instruct patients to take two separate doses in conjunction with liquids, as follows: dose 1 – on the day before colonoscopy: instruct patients to consume only clear liquids (no solid food or dairy) on the day before the colonoscopy up until 2 hours before the time of the colonoscopy. take the first dose (1 bottle) of clenpiq during the evening before the colonoscopy (e.g., 5:00 pm to 9:00 pm). follow clenpiq by drinking five or more 8-ounce cups (cup provided) of clear liquids within 5 hours and before bed. if severe bloating, distention, or abdominal pain occurs, following the first dose, delay the second dose until the symptoms resolve. dose 2 – next morning on the day of colonoscopy (start approximately 5 hours prior to colonoscopy): continue to consume only clear liquids (no solid food or dairy). take the second dose (the second bottle) of clenpiq. following the clenpiq dose, drink four or more 8-ounce cups (cup provided) of clear liquids up to 2 hours before the colonoscopy.

1-800-fda-1088 or www.fda.gov/medwatch. 6.1 clinical trials experience because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice. adults clinical study of clenpiq - study 1 table 1 displays the most common adverse reactions in a randomized, multicenter, assessor-blinded, non-inferiority trial of clenpiq for colon cleansing in adults (study 1). clenpiq was compared to another oral sodium picosulfate, magnesium oxide, and anhydrous citric acid product, both administered according to the split-dose dosing regimen [see clinical studies (14) ] . table 1: common adverse reactions observed in at least 2% of patients undergoing colon cleansing in study 1 adverse reaction split-dose regimen clenpiq (n=448) % sodium picosulfate, magnesium oxide, and anhydrous citric acid powder for reconstitution (n=453) % nausea 3 3 headache 3 3 hypermagnesemia magnesium levels returned to normal within one week after colonoscopy in all patients in the clenpiq group. 2 5 abdominal pain abdominal pain included reports of abdominal pain, abdominal pain upper, and abdominal pain lower. 2 2 dehydration or dizziness 2 2 clinical study of another sodium picosulfate, magnesium oxide and anhydrous citric acid product - study 2 in a randomized, multicenter, investigator-blinded, active-controlled clinical trial for colon cleansing in adults, another oral sodium picosulfate, magnesium oxide, and anhydrous citric acid product was compared with a regimen of two liters (2 l) of polyethylene glycol plus electrolytes solution (peg + e) and two 5-mg bisacodyl tablets (study 2). in this study the protocol specified that abdominal bloating, distention, pain/cramping, and watery diarrhea, which are known to occur in response to bowel preparation, were documented as adverse events only if they required medical intervention (such as a change in study drug or led to discontinuation, therapeutic or diagnostic procedures, met the criteria for serious adverse event) or showed clinically significant worsening during the study that was not in the frame of the usual clinical course, as determined by the investigator. the most common adverse reactions in study 2 are shown in table 2. table 2: common adverse reactions abdominal bloating, distention, pain/cramping, and watery diarrhea not requiring an intervention were not collected observed in at least 1% of patients undergoing colon cleansing in study 2 adverse reaction split-dose regimen sodium picosulfate, magnesium oxide, and anhydrous citric acid (n=305) % 2 l peg + e 2 l peg + e = two liters polyethylene glycol plus electrolytes solution with 2 × 5-mg bisacodyl tablets (n=298) % nausea 3 4 headache 2 2 vomiting 1 3 electrolyte abnormalities in study 1, rates of abnormal electrolyte shifts were generally similar between clenpiq and another sodium picosulfate, magnesium oxide, and anhydrous citric acid product (table 3). in general, these shifts were transient and not clinically significant. in study 2, sodium picosulfate, magnesium oxide, and anhydrous citric acid was in general associated with numerically higher rates of abnormal electrolyte shifts on the day of colonoscopy compared to the control regimen (table 3). these shifts were transient in nature and numerically similar between treatment arms at the day 28 visit. table 3: shifts from normal baseline to outside the normal range post-baseline laboratory parameter (direction of change) visit split-dose regimen study 1 split-dose regimen study 2 clenpiq sodium picosulfate, magnesium oxide, and anhydrous citric acid powder for reconstitution sodium picosulfate, magnesium oxide, and anhydrous citric acid 2 l peg+e with 2 × 5 mg bisacodyl tablets n/n (%) n/n (%) n/a: not applicable. potassium (low) day of colonoscopy 34/422 (8.1) 10/423 (2.4) 19/260 (7.3) 11/268 (4.1) 24-48 hours 13/417 (3.1) 3/423 (0.7) 3/302 (1.0) 2/294 (0.7) day 7 7/420 (1.7) 6/425 (1.4) 11/285 (3.9) 8/279 (2.9) day 28 3/421 (0.7) 7/423 (1.7) 11/284 (3.9) 8/278 (2.9) sodium (low) day of colonoscopy 4/426 (0.9) 23/443 (5.2) 11/298 (3.7) 3/295 (1.0) 24-48 hours 6/423 (1.4) 9/441 (2.0) 1/303 (0.3) 1/295 (0.3) day 7 6/423 (1.4) 9/440 (2.0) 2/300 (0.7) 1/292 (0.3) day 28 8/427 (1.9) 9/439 (2.1) 2/299 (0.7) 3/291 (1.0) chloride (low) day of colonoscopy 23/437 (5.3) 16/444 (3.6) 11/301 (3.7) 1/298 (0.3) 24-48 hours 3/434 (0.7) 3/442 (0.7) 1/303 (0.3) 0/295 (0.0) day 7 3/434 (0.7) 2/441 (0.5) 1/303 (0.3) 3/295 (1.0) day 28 4/438 (0.9) 1/440 (0.2) 2/302 (0.7) 3/294 (1.0) magnesium (high) day of colonoscopy 112/431 (26.0) 143/440 (32.5) 34/294 (11.6) 0/294 (0.0) 24-48 hours 23/427 (5.4) 21/440 (4.8) 0/303 (0.0) 0/295 (0.0) day 7 11/428 (2.6) 9/440 (2.0) 0/297 (0.0) 1/291 (0.3) day 28 10/432 (2.3) 12/438 (2.7) 1/296 (0.3) 2/290 (0.7) calcium (low) day of colonoscopy 8/436 (1.8) 1/446 (0.2) 2/292 (0.7) 1/286 (0.3) 24-48 hours 1/434 (0.2) 0/444 (0.0) 0/303 (0.0) 0/295 (0.0) day 7 0/434 (0.0) 0/444 (0.0) 0/293 (0.0) 1/283 (0.4) day 28 0/439 (0.0) 2/442 (0.5) 0/292 (0.0) 1/282 (0.4) bicarbonate (low) day of colonoscopy 6/431 (1.4) 35/438 (8.0) n/a bicarbonate was not analyzed in study 2. n/a 24-48 hours 40/430 (9.3) 43/434 (9.9) n/a n/a day 7 37/430 (8.6) 40/438 (9.1) n/a n/a day 28 33/433 (7.6) 43/436 (9.9) n/a n/a creatinine (high) day of colonoscopy 6/427 (1.4) 1/432 (0.2) 5/260 (1.9) 13/268 (4.9) 24-48 hours 6/425 (1.4) 5/431 (1.2) 1/303 (0.3) 0/295 (0.0) day 7 5/426 (1.2) 4/431 (0.9) 10/264 (0.4) 13/267 (4.8) day 28 4/429 (0.9) 6/429 (1.4) 11/264 (4.2) 14/265(5.3) pediatrics in the pediatric patients aged 9 to 16 years who received another oral product of sodium picosulfate, magnesium oxide, and anhydrous citric acid, the most common adverse reactions (> 5%) were nausea, vomiting, and abdominal pain [see clinical studies (14) ] . electrolytes abnormalities were observed in pediatric patients similar to those seen in adults. three patients had abnormally low glucose levels (40 to 47 mg/dl). two patients received sodium picosulfate, magnesium oxide, and anhydrous citric acid and one received the comparator (peg). the abnormal values occurred at the colonoscopy visit for one patient (sodium picosulfate, magnesium oxide, and anhydrous citric acid) and at the 5-day follow up visit for the other two patients (sodium picosulfate, magnesium oxide, and anhydrous citric acid and peg). all three patients were asymptomatic. 6.2 postmarketing experience the following adverse reactions have been identified during post approval use of oral sodium picosulfate, magnesium oxide, and anhydrous citric acid products. because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. hypersensitivity : rash, urticaria, and purpura gastrointestinal: abdominal pain, diarrhea, fecal incontinence, proctalgia, vomiting, reversible aphthoid ileal ulcers, and ischemic colitis [see warnings and precautions (5.5) ] neurologic: generalized tonic-clonic seizures with and without hyponatremia in epileptic patients [see warnings and precautions (5.2) ] .

ation with magnesium. 7.3 antibiotics prior or concomitant use of antibiotics with clenpiq may reduce efficacy of clenpiq as conversion of sodium picosulfate to its active metabolite bhpm is mediated by colonic bacteria.

administration of up to 2000 mg/kg twice daily (about 1.2 times the recommended human dose based on body surface area) during the period of organogenesis. there was no evidence of harm to the fetus due to sodium picosulfate, magnesium oxide, and anhydrous citric acid. the reproduction study in rabbits was not adequate, as treatment-related mortalities were observed at all doses. a pre and postnatal development study with sodium picosulfate, magnesium oxide, and anhydrous citric acid in rats showed no evidence of any adverse effect on pre and postnatal development at oral doses up to 2000 mg/kg twice daily (about 1.2 times the recommended human dose based on body surface area). published reproduction studies with sodium picosulfate in pregnant rats and rabbits during the period of organogenesis did not show evidence of harm to the fetus at doses up to 100 mg/kg (approximately 49 and 98 times, respectively, the recommended human dose of 10 mg sodium picosulfate based on body surface area). 8.2 lactation risk summary there are no data on the presence of magnesium oxide or anhydrous citric acid in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. published data on lactating women indicate that the active metabolite of sodium picosulfate, bis-( p -hydroxyphenyl)-pyridyl-2-methane (bhpm) remained below the limit of detection (1 ng/ml) in breast milk after both single and multiple doses of 10 mg/day. there are no data on the effects of sodium picosulfate on the breastfed infant or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for clenpiq and any potential adverse effects on the breastfed infant from clenpiq or the underlying maternal condition. 8.4 pediatric use the safety and effectiveness of clenpiq have been established for cleansing of the colon as a preparation for colonoscopy in pediatric patients 9 years of age and older. use of clenpiq in this age group is supported by evidence from adequate and well-controlled trials in adults and a single, dose-ranging, controlled trial in 78 pediatric patients 9 to 16 years of age all of which evaluated another oral product of sodium picosulfate, magnesium oxide, and anhydrous citric acid [see clinical studies (14) ]. the safety profile in this pediatric population was similar to that seen in adults [see adverse reactions (6.1) ] . monitor for possible hypoglycemia in pediatric patients, as clenpiq has no caloric substrate. the safety and effectiveness of clenpiq in pediatric patients less than 9 years of age have not been established. 8.5 geriatric use of the 448 adult patients in study 1 who received clenpiq, 124 (28%) patients were 65 years of age or older. no overall differences in safety or effectiveness were observed between geriatric patients and younger patients, and other reported clinical experience has not identified differences in responses between elderly and younger patients. elderly patients are more likely to have decreased hepatic, renal, or cardiac function and may be more susceptible to adverse reactions resulting from fluid and electrolyte abnormalities [see warnings and precautions (5.1) ]. 8.6 renal impairment clenpiq is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 ml/min), as accumulation of magnesium in plasma may occur [see contraindications (4) ] . patients with less severe renal impairment or patients taking concomitant medications that may affect renal function may be at increased risk for renal injury [see warnings and precautions (5.3) ] . advise these patients of the importance of adequate hydration before, during, and after the use of clenpiq [see dosage and administration (2.1) ] . consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and bun) in these patients.

g/kg twice daily (about 1.2 times the recommended human dose based on body surface area) during the period of organogenesis. there was no evidence of harm to the fetus due to sodium picosulfate, magnesium oxide, and anhydrous citric acid. the reproduction study in rabbits was not adequate, as treatment-related mortalities were observed at all doses. a pre and postnatal development study with sodium picosulfate, magnesium oxide, and anhydrous citric acid in rats showed no evidence of any adverse effect on pre and postnatal development at oral doses up to 2000 mg/kg twice daily (about 1.2 times the recommended human dose based on body surface area). published reproduction studies with sodium picosulfate in pregnant rats and rabbits during the period of organogenesis did not show evidence of harm to the fetus at doses up to 100 mg/kg (approximately 49 and 98 times, respectively, the recommended human dose of 10 mg sodium picosulfate based on body surface area).

ses separated by 6 hours, the mean ± sd plasma c max for picosulfate of 3.2 ± 2.6 ng/ml was reached at approximately 7 hours after the first dose administration. in the same study, the uncorrected plasma magnesium concentration reached a c max of approximately 1.9 meq/l at 10 hours after the first dose administration, which represents an approximately 20% increase from baseline. in patients scheduled to have an elective colonoscopy who received the split-dose dosing regimen of clenpiq, the mean ± sd plasma concentration for picosulfate was 1.05 ± 0.83 ng/ml at 15 minutes pre-second dose, 2.98 ± 1.27 ng/ml at 1-2 hours post-second dose, and 1.81 ± 0.86 ng/ml at 3-6 hours post-second dose. metabolism and elimination metabolism and excretion plasma concentrations of the free bhpm were below the lower limit of quantification (0.1 ng/ml) in 13 out of 16 subjects studied. the fraction of the sodium picosulfate dose excreted unchanged in urine was 0.1%. in urine, the majority of excreted bhpm was in the glucuronide-conjugated form. the terminal half-life of sodium picosulfate was 7.4 hours. use in specific populations pediatric patients pharmacokinetics of picosulfate was studied in pediatric patients aged from 9 to 16 years old. the half-life of picosulfate was 7 hours. the picosulfate reached the mean ± sd c max of 3.5 ± 2.1 ng/ml at approximately 6 to 7 hours. the baseline uncorrected mean serum magnesium concentration was 2.02 meq/l at 10 hours after the first dose of sodium picosulfate, magnesium oxide, and anhydrous citric acid and ranged from 1.7 to 2.46 meq/l. drug interaction studies in an in vitro study using human liver microsomes, sodium picosulfate did not inhibit the major cyp enzymes (cyp 1a2, 2b6, 2c8, 2c9, 2c19, 2d6, and 3a4/5) evaluated. based on an in vitro study using freshly isolated hepatocyte culture, sodium picosulfate is not an inducer of cyp1a2, cyp2b6, or cyp3a4/5.

± 0.86 ng/ml at 3-6 hours post-second dose. metabolism and elimination metabolism and excretion plasma concentrations of the free bhpm were below the lower limit of quantification (0.1 ng/ml) in 13 out of 16 subjects studied. the fraction of the sodium picosulfate dose excreted unchanged in urine was 0.1%. in urine, the majority of excreted bhpm was in the glucuronide-conjugated form. the terminal half-life of sodium picosulfate was 7.4 hours. use in specific populations pediatric patients pharmacokinetics of picosulfate was studied in pediatric patients aged from 9 to 16 years old. the half-life of picosulfate was 7 hours. the picosulfate reached the mean ± sd c max of 3.5 ± 2.1 ng/ml at approximately 6 to 7 hours. the baseline uncorrected mean serum magnesium concentration was 2.02 meq/l at 10 hours after the first dose of sodium picosulfate, magnesium oxide, and anhydrous citric acid and ranged from 1.7 to 2.46 meq/l. drug interaction studies in an in vitro study using human liver microsomes, sodium picosulfate did not inhibit the major cyp enzymes (cyp 1a2, 2b6, 2c8, 2c9, 2c19, 2d6, and 3a4/5) evaluated. based on an in vitro study using freshly isolated hepatocyte culture, sodium picosulfate is not an inducer of cyp1a2, cyp2b6, or cyp3a4/5.

a total of 901 adult patients were included in the primary efficacy analysis. patients ranged in age from 20 to 80 years (mean age 57 years); 56% were female and 44% male. self-identified race was approximately distributed as follows: 85% white, 10% black, 2% asian, and 3% other. approximately 15% of patients self-identified their ethnicity as hispanic or latino. the primary efficacy endpoint was the proportion of patients with successful overall colon cleansing, as assessed by blinded colonoscopists using the modified aronchick scale. the modified aronchick scale is a validated tool used to assess overall colon cleansing prior to suctioning or cleaning. successful colon cleansing was defined as bowel preparations with >90% of the mucosa seen and mostly liquid stool that were graded excellent (minimal suctioning needed for adequate visualization) or good (significant suctioning needed for adequate visualization) by the colonoscopist. in the trial, clenpiq was non-inferior and also met the pre-specified criteria for superiority to the comparator for overall colon cleansing. efficacy results are provided in table 4. table 4: proportion of patients with successful colon cleansing according to the modified aronchick scale in study 1 using the split-dose regimen clenpiq sodium picosulfate, magnesium oxide, and anhydrous citric acid powder for reconstitution difference between treatment groups difference and 95% ci are based on stratified difference in proportions, where the stratification weight is based on cochran-mantel-haenszel weight. % (n/n) % (n/n) difference 95% ci 87.7% (393/448) 81.5% (369/453) 6.3% (1.8%, 10.9%) non-inferior and superior to sodium picosulfate, magnesium oxide, and anhydrous citric acid clinical study of another oral sodium picosulfate, magnesium oxide and anhydrous citric acid product – study 2 the colon cleansing efficacy of another oral sodium picosulfate, magnesium oxide, and anhydrous citric acid product was evaluated in a randomized, investigator-blinded, active-controlled, multicenter us non-inferiority trial in adult patients scheduled to have an elective colonoscopy (nct01073930). patients were randomized to sodium picosulfate, magnesium oxide, and anhydrous citric acid group or polyethylene glycol plus electrolytes (peg + e) and bisacodyl. sodium picosulfate, magnesium oxide, and anhydrous citric acid was given by "split-dose" (evening before and day of) dosing, where the first dose was taken the evening before the colonoscopy (between 5:00 and 9:00 pm), followed by five (5) 8-ounce glasses of clear liquid, and the second dose was taken the morning of the colonoscopy (at least 5 hours prior to but no more than 9 hours prior to colonoscopy), followed by three (3) 8-ounce glasses of clear liquid. the comparator was given as two liters of polyethylene glycol plus electrolytes solution (peg + e) and two 5-mg bisacodyl tablets, administered the day before the procedure. all patients in both treatment groups were limited to a clear liquid diet on the day before the procedure (24 hours before). a total of 601 adult patients were included in the primary efficacy analysis. patients ranged in age from 18 to 80 years (mean age 55 years); 59% were female and 41% male. self-identified race was distributed as follows: 88% white, 10% black, and less than 2% other. of these, 2% self-identified their ethnicity as hispanic or latino. the primary efficacy endpoint was the proportion of patients with successful colon cleansing, as assessed by blinded colonoscopists using the aronchick scale. the aronchick scale is a tool used to assess overall colon cleansing. successful colon cleansing was defined as bowel preparations with >90% of the mucosa seen and mostly liquid stool that were graded excellent (minimal suctioning needed for adequate visualization) or good (significant suctioning needed for adequate visualization) by the colonoscopist. sodium picosulfate, magnesium oxide, and anhydrous citric acid was non-inferior to the comparator. in addition, sodium picosulfate, magnesium oxide, and anhydrous citric acid met the pre-specified criteria for superiority to the comparator for colon cleansing. efficacy results are provided in table 5. table 5: proportion of patients with successful colon cleansing in study 2 sodium picosulfate, magnesium oxide, and anhydrous citric acid 2 l peg+e 2 l peg + e = two liters polyethylene glycol plus electrolytes solution. with 2 × 5-mg bisacodyl tablets difference between treatment groups % (n/n) % (n/n) difference 95% ci 84% (256/304) 74% (221/297) 10% (3.4%, 16.2%) non-inferior and superior to 2 l peg+e with 2 × 5-mg bisacodyl tablets pediatric patients 9 years of age and older the safety and efficacy of clenpiq in pediatric patients 9 years of age and older has been established based on another oral product of sodium picosulfate, magnesium oxide and anhydrous citric acid provided in powder packets for reconstitution (nct01928862). sodium picosulfate, magnesium oxide, and anhydrous citric acid was evaluated for colon cleansing in a randomized, assessor-blind, multicenter, dose-ranging, active-controlled study in 78 pediatric patients 9 years to 16 years of age. the majority of patients were female (68%), white (91%), and of non-hispanic or non-latino ethnicity (95%). the mean age was 12 years of age. all 78 patients were included in the primary efficacy analysis. patients aged 9 years to 12 years were randomized into 3 arms (1:1:1): sodium picosulfate, magnesium oxide, and anhydrous citric acid one-half packet per dose administered as two doses sodium picosulfate, magnesium oxide, and anhydrous citric acid one packet per dose administered as two doses comparator (oral peg-based solution per local standard of care). patients aged 13 years to 16 years were randomized into 2 arms (1:1): sodium picosulfate, magnesium oxide, and anhydrous citric acid one packet per dose administered as two doses comparator (oral peg-based solution per local standard of care) patients randomized to sodium picosulfate, magnesium oxide, and anhydrous citric acid had two options for dosing, as determined by the investigator. the "split-dose" regimen was the preferred method and the "day-before" regimen was the alternative method if the "split-dose" was not appropriate. "split-dose" regimen: (evening before and day of) dosing, where the first dose was taken the evening before the colonoscopy (between 5:00 and 9:00 pm), followed by five (5) 8-ounce glasses of clear liquid, and the second dose was taken the morning of the colonoscopy (at least 5 hours prior to but no more than 9 hours prior to colonoscopy), followed by three (3) 8-ounce glasses of clear liquid. "day-before" regimen: (afternoon/evening before only) dosing, where both doses were taken separately on the day before the colonoscopy, with the first dose taken in the afternoon (between 4:00 and 6:00 pm), followed by five (5) 8-ounce glasses of clear liquid, and the second dose taken in the late evening (approximately 6 hours later, between 10:00 pm and 12:00 am), followed by three (3) 8-ounce glasses of clear liquid. all patients randomized to sodium picosulfate, magnesium oxide, and anhydrous citric acid was limited to a clear liquid diet on the day before the procedure. those who received the comparator were given dietary instructions per the trial site's standard of care. the primary efficacy endpoint was the proportion of patients with successful colon cleansing as defined as a rating of either "excellent" (> 90% of mucosa seen, mostly liquid stool, minimal suctioning needed for adequate visualization) or "good" (> 90% of mucosa seen, mostly liquid stool, significant suctioning needed for adequate visualization) using the aronchick scale, as assessed by blinded colonoscopists. the sodium picosulfate, magnesium oxide, and anhydrous citric acid regimen of one-half packet per dose administered as two doses did not demonstrate comparable efficacy to the comparator, peg, in patients 9 to 12 years of age and is not a clenpiq recommended dosage regimen [see dosage and administration (2) ] . the sodium picosulfate, magnesium oxide, and anhydrous citric acid regimen of one packet per dose administered as two doses demonstrated successful colon cleansing in both the 9 to 12 year age group and the 13 to 16 year age group. the efficacy rates were similar to those observed in the peg groups, as shown in table 6. table 6. proportion of patients 9 to 16 years of age with successful colon cleansing successful colon cleansing as defined by "excellent" or "good" on the aronchick scale sodium picosulfate, magnesium oxide, and anhydrous citric acid, one packet administered as two doses either as split dose or day before regimen of the 32 patients, 9 received the split dose regimen and 23 the day before regimen peg comparator oral peg-based preparation was used in the study as per standard of care % (n/n) 95% ci % (n/n) 95% ci age 9-12 88% (14/16) (62, 98) 81% (13/16) (54, 96) age 13-16 81% (13/16) (54, 96) 86% (12/14) (57, 98)

regimen, as prescribed. to consume additional liquids after each dose of clenpiq: five or more 8-ounce cups of clear liquids after the first dose and four or more 8-ounce cups of clear liquids after the second dose. to delay the second dose of clenpiq, if severe bloating, distention, or abdominal pain occurs following the first dose until the symptoms resolve. to contact their healthcare provider if they develop significant vomiting or signs of dehydration after taking clenpiq or if they experience altered consciousness (e.g. confusion, delirium, loss of consciousness) or seizures [see warnings and precautions (5.1 , 5.2 , 5.4) ] .